Summary

Major depression disorder (MDD) is a frequent and disabling mental disorder with great risk
of recurrence and chronicity. Interpersonal factors are among the strongest predictors of
the course and duration of an episode of depression. More specifically, social rejection is
one of the most environmental risk factors of MDD. Targeted rejection predicts hastened
onset of major depression. On the other hand, healthy subject show prosocial behavior after
social rejection to reconnect to new source of social interaction. In addition to the
potential impact of social exclusion on MDD onset, depressed patients may be more prone to
be rejected as they encounter interpersonal difficulties and may less be able to reconnect
to the social group after rejection.

Recent neuroimaging data show that brain processing of social exclusion activate brain
regions that are central to the pathophysiology of MDD. Some of these regions are also known
to be activated during physical pain and may contribute to the aversive dimension of the
experienced rejection. Pro-inflammatory cytokines are involved in MDD physiopathology and
can induce social withdrawal behavior. Inflammation can modulate social interactions in
mammals. Moreover, after a social stress such as social rejection, blood cytokines increase.
At a cognitive level, self-esteem can modulate the sensitivity to social rejection.

The major objective of the trial is to study sensitivity to social signals in MDD patient
compared to healthy subject.

Secondary objective is to identify psychological and biological mediators We hypothetize in
MDD patient: (1)mediating effect of systemic inflammatory cytokines, an (2) mediating effect
of state self esteem 30 MDD patients and 60 healthy subject will be included. They will
encounter psychiatric and psychometric evaluation. Their facial EMG will be recorded to
assess RFR to dynamic emotional faces created by photo morphing from KDEF emotional faces
database, coupled to occulometric recording. Subjects will perform cyberball game as an
experimental inclusion or exclusion task and the trustgame task as an implicit evaluation of
their prosocial behavior. Questionnaires will assess explicit measurement of social
rejection pain and desire of affiliation. Inflammatory markers will be measured in a blood
sample before the cyberball task for every subjects and 6 hours later for 20 healthy
volunteers. Dosage of IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF,
Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 will be performed by luminex technique and usCRP,
srIL2 ans sCD14 by ELISA technique.